Cortactin as a potential predictor of second esophageal neoplasia in hypopharyngeal carcinoma

Abstract

Objective

Hypopharyngeal carcinoma has a very poor prognosis. The high incidence of second esophageal neoplasia is one of the major causes. To establish an efficient follow-up scheme for increasing the diagnostic yield and reducing the adverse impact of second esophageal neoplasia on survival, the purpose of this study was to explore a biomarker to predict second esophageal neoplasia.

Methods

In this retrospective cohort study, consecutive tissue specimens from those patients who underwent tumor resection between September 2007 and October 2015 were collected. Gene amplification was performed by real-time PCR. The expression of cortactin was evaluated by immunohistochemistry. The predictive risk factors of developing second esophageal neoplasia and prognostic factors related to survival were analyzed.

Results

A total of 187 patients were included with a mean follow-up of 48 months (12–118 months). Second esophageal tumors were found in 53 (28.3%), including 41 (21.9%) esophageal squamous cell carcinoma and 12 severe dysplasia. The results of multivariate analyses revealed that age (OR 2.81, 95% CI 1.16–6.78), cortactin overexpression (OR 2.49, 95% CI 1.17–5.33), and stage IV versus I (OR 6.49, 95% CI 1.68–25.18) were independent predictors of second esophageal neoplasia, and second esophageal neoplasia (HR 1.78, 95% CI 1.05–3.01) was an independent predictor of overall survival.

Conclusion

This is the first report to identify a potential biomarker for predicting second esophageal neoplasia in patients with hypopharyngeal carcinoma. In those patients with cortactin overexpression and younger age (≤60 years old), close surveillance for second esophageal neoplasia is required. In addition, the real effect of cortactin overexpression on development of primary esophageal carcinoma is required to be validated in a large cohort study.

Introduction

Head and neck squamous cell carcinoma (HNSCC) mainly includes carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx, of which hypopharyngeal squamous cell carcinoma (HPC) has the worst prognosis [1], [2]. The high incidence rate of second esophageal tumors is one of the major causes [3]. Most of the HPC patients have habits of cigarette smoking, alcohol consumption, and betel nut chewing, and these habits also increase the risk of developing esophageal and oral cancers [4], [5], [6], [7]. For further understanding the disease of second esophageal cancers, predictive factors including demographic and clinicopathological factors in HNSCC have been studied, and alcohol drinker and tumor site (oropharyngeal or hypopharyngeal cancer) have been found significant predictors [4], [8]. In addition to clinicopathological predictors, early detection of esophageal tumors by image-enhanced endoscopy has also been published [9].

Cortactin is encoded by the CTTN (also called EMS1) gene located on chromosome 11q13. EMS1 gene amplification is correlated with tumor grade, lymph node metastasis, tumor recurrence, and decreased overall survival [10]. Cortactin overexpression has consistently associated with carcinogenesis, invasiveness, and poor prognosis in HNSCC and other malignancies [11], [12], [13], [14], [15]. In esophageal carcinoma, an association between cortactin overexpression (CTTN or EMS1 gene amplification) and carcinogenesis has been reported in two articles [16], [17]. However, no further clinical validation and analysis for the relation between cortactin expression status and esophageal neoplasia have ever been demonstrated. Because a high rate of second esophageal neoplasia has been found in patients with HNSCC [18], which is critical to disease survival, it is mandatory to detect the disease as early as possible. Furthermore, the incidence of second primary tumors has been reported to be constant for over 10 years [19], so identifying risk factors for second primary tumors is an efficient way to prevent unnecessary examinations.

To establish an efficient follow-up scheme, this study was performed to detect a relationship between second esophageal neoplasia and cortactin overexpression (and other factors), and to understand the impact of second esophageal neoplasia on overall survival (OS).